Abstract
Membrane lipid rafts are sphingolipids and cholesterol-enriched membrane microdomains, which form a center for the interaction or assembly of palmitoylated signaling molecules, including Src family non-receptor type protein tyrosine kinases. Lipid rafts abundantly exist in neurons and function in the maintenance of synapses. Excitatory synaptic strength is largely controlled by the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors in the mammalian brain. AMPA receptor endocytosis from the synaptic surface is regulated by phosphorylation of the GluA2 subunit at tyrosine 876 by Src family kinases. Here, I revealed that tyrosine phosphorylated GluA2 is concentrated in the lipid rafts fraction. Furthermore, stimulation-induced upregulation of GluA2 tyrosine phosphorylation is disrupted by the treatment of neurons with a cholesterol-depleting compound, filipin III. These results indicate the importance of lipid rafts as enzymatic reactive sites for AMPA receptor tyrosine phosphorylation and subsequent AMPA receptor internalization from the synaptic surface.
Introduction
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Glutamate receptors (GluRs) majorly mediate fast excitatory synaptic transmission in the brain (Seeburg, 1993; Hollmann and Heinemann, 1994; Mori and Mishina, 2003). Excitatory synaptic strength is largely controlled by dynamic changes of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type GluRs (AMPA receptors) expression on the synaptic surface, especially by a balance between rapid insertion of intracellular AMPA receptors into the surface and internalization of surface-expressing AMPA receptors in a stimulation-dependent manner (Collingridge et al., 2004; Kessels and Malinow, 2009; Huganir and Nicoll, 2013). AMPA receptors are composed of four subunits, GluA1–4 (also known as GluR1–4, GluRA–D, or GluRα1–4). Major functional AMPA receptors in the adult CNS comprise GluA1/GluA2- and GluA2/GluA3-containing receptors (Shepherd and Huganir, 2007; Heine et al., 2008; Henley and Wilkinson, 2016; Diering and Huganir, 2018). The GluA2 subunit is the primary determinant during endocytosis from synapses and post-endocytic endosomal sorting (Anggono and Huganir, 2012; Diering and Huganir, 2018).
Previous studies have revealed that trafficking processes of AMPA receptors are regulated by several post-translational protein modifications of the AMPA receptor subunits, including reversible phosphorylation, and S-palmitoylation of them (Jiang et al., 2006; Anggono and Huganir, 2012; Lu and Roche, 2012; Parkinson and Hanley, 2018). Among those dynamic modifications, tyrosine phosphorylation of the GluA2 subunit enhances AMPA receptors internalization from the synaptic surface (Hayashi and Huganir, 2004; Gladding et al., 2009; Hu et al., 2010; Yong et al., 2020). We have shown that Src family protein tyrosine kinases (PTKs) catalyze tyrosine phosphorylation of GluA2 at tyrosine 876 (Hayashi and Huganir, 2004). GluA2 tyrosine phosphorylation induces an exchange of GluA2-binding scaffolding proteins from glutamate receptor-interacting proteins 1/2 (GRIP1/2) to protein interacting with C-kinase (PICK1), which sequentially drives endocytosis of surface AMPA receptors (Hayashi and Huganir, 2004; Yong et al., 2020). Furthermore, the interaction of GluA2 with the synaptic protein BRAG2, a guanine-nucleotide exchange factor (GEF) for the coat-recruitment GTPase Arf6, occurs in a GluA2 tyrosine phosphorylation-dependent manner, which induces the AMPA receptor endocytosis in long-term synaptic depression (Scholz et al., 2010).
Src family PTKs are palmitoylated and myristoylated at their N-terminal regions (Neet and Hunter, 1996). Covalent attachments of saturated fatty acids, 16-carbon containing palmitate and 14-carbon containing myristate, on the non-receptor type PTKs generally increase their affinity to membrane fraction and induce their translocation from cytosolic region to membrane (Nadolski and Linder, 2007; Resh, 2016). Furthermore, accumulating evidence indicates that these protein lipidations enable signaling molecules to limitedly localize in a specific lipid microdomain in the cellular membrane, termed lipid rafts (Simons and Vaz, 2004; Turner et al., 2005; Pike, 2006). Lipid rafts are primarily sphingolipids and cholesterol-enriched dynamic membrane microdomains, which have been proposed as a center for the interaction or assembly of palmitoylated signaling molecules, including Src family PTKs, G-proteins, and various membrane receptors (Kasahara et al., 2000; Moffett et al., 2000; Foster et al., 2003; Fujita et al., 2007). The brain is the organ with the highest enrichment in lipids, including sphingolipids and cholesterol (Aureli et al., 2015; Schnaar, 2016). Lipid rafts abundantly exist in the dendrites of neurons and function in the maintenance of synapses as well as in the stabilization of surface AMPA receptors (Hering et al., 2003). Here, I present that the lipid rafts structure is essential for GluR agonist-induced tyrosine phosphorylation of GluA2, which exhibits the importance of lipid rafts as enzymatic reactive sites for Src family PTKs-mediated AMPA receptor modification.
Materials and methods
Drugs and antibodies
Filipin III and Optiprep™, a non-ionic iodixanol-based density gradient medium, were purchased from Sigma-Aldrich (St. Louis, MO, USA). Anti-GluA2 N-terminal monoclonal antibody (MAB397, Chemicon, Temecula, CA, USA), anti-GluA2 phospho tyrosine 876 polyclonal antibodies (JH3410, Hayashi and Huganir, 2004; Hu et al., 2010; Yong et al., 2020), anti-Fyn monoclonal antibody (F19720, Transduction Laboratories, Lexington, KY, USA), and anti-Caveolin1 polyclonal antibodies (N-20, sc-894, Santa Cruz Biotechnology, Santa Cruz, CA, USA) were used for the experiments.
Primary neuron culture and stimulation
High-density cultured cortical neurons were prepared on poly-L-lysine coated culture dishes of 60 mm diameter dish as described previously (Hayashi and Huganir, 2004). Cultured cortical neurons (106 cells per lane) were used between 3 and 4 weeks [at 24, 29, 31, and 34 days in vitro (DIV)] after plating for biochemical experiments. For stimulation of AMPA receptors, cortical culture neurons at 25–26 days DIV were washed three times with 3 ml of extracellular artificial cerebrospinal fluid (aCSF) solution containing 15 mM HEPES, pH 7.5, 140 mM NaCl, 5 mM KCl, 1 mM MgCl2, 5 mM glucose, 0.5 mM EDTA, and 0.12% NaHCO3. The extracellular solution was replaced by a 2 ml aCSF solution containing 5 μM TTX to inhibit neuronal activity. Then, cultured cortical neurons were treated with or without 10 μg/ml Filipin III and incubated in the same buffer at 37°C for 10 min before stimulation with 100 μM AMPA for 10 min. An amount of 2.5 mg/ml of Filipin III dissolved in DMSO was prepared at the time of use as a stock solution, and 8 μl Filipin III (final 10 μg/ml) solution or DMSO was added to extracellular solutions of cultured cortical neurons (Gimpl et al., 1997; Foster et al., 2003; Lambert et al., 2006).
Analysis of proteins
Neurons were lysed in 1.2 ml buffer containing 50 mM Tris–HCl, pH8.0, 1% Triton X-100, 150 mM NaCl, 20 mM EDTA, 1 mM Na3VO4, 100 μg/ml phenylmethylsulfonyl fluoride (PMSF), 2 μg/ml aprotinin, 1 μg/ml pepstatin, and 0.5 μg/ml leupeptin. Homogenates were centrifuged at 15,000 × g for 20 min at 4°C. Lysates were separated by 7.5% SDS-PAGE, followed by Western blotting with each antibody. Blocking and washing solutions for immunoblotting were 5% skim milk and 0.1% Tween-20 in tris-buffered saline (TBS) (50 mM Tris–HCl, pH 7.5, and 150 mM NaCl) and TBS containing 0.05% Triton X-100, respectively. Reactive bands were visualized with the electrochemiluminescence (ECL). Chemiluminescent images were acquired using the ImageQuant LAS 4000 mini imager (GE Healthcare, Tokyo, Japan). The phosphorylation ratio was estimated by comparing the intensity of each band: tyrosine phosphorylated GluA2 to total GluA2 protein amount in the cultured neurons and control without filipin III treatment was defined as 100%.
Density gradient fractionation
Cultured neurons at 27–35 DIV were washed twice with 1.0 ml cold phosphate-buffered saline (PBS) and scraped in 1.5 ml buffer containing 20 mM Tris–HCl, pH7.5, 250 mM Sucrose, 50 mM NaCl, 1 mM DTT, 1 mM Na3VO4, a cocktail of protease inhibitors. Collected neurons were mechanically homogenized on ice by five passages through a 22G syringe needle, followed by centrifugation at 1,000 × g for 10 min at 4°C. The pellets were resuspended in 0.5 ml buffer and repeatedly homogenized by five passages through the 22G syringe needle and centrifugation. Combined 2.0 ml supernatants were adjusted to 35% Optiprep in a total of 4.8 ml and overlaid with 2.5 ml of each 30, 20, and 5% Optiprep prepared in the same buffer. The gradients were spun at 40,000 rpm for 3 h at 4°C in an SW41 rotor using a Beckman ultracentrifuge. The interface 5 and 20% boundary (900 μl) was collected, followed by the addition of two-thirds volume (600 μl) of the same buffer containing 1.25% Triton X-100 (final 0.5%), and lysed for 60 min at 4°C with rotation. Then, lysates were adjusted to 35% Optiprep in a totally of 3.6 ml and overlaid with 7.5 ml of 30% Optiprep and 1.5 ml of 0% Optiprep prepared in the same buffer containing 0.1% Triton X-100, 1 mM Na3VO4. The gradients were spun at 40,000 rpm for 5 h at 4°C in the SW41 rotor. Six fractions were collected from top to bottom of centrifuge tubes (Smart et al., 1995; Lafont et al., 1998, 1999; Oliferenko et al., 1999; Lindwasser and Resh, 2001; Inoue et al., 2004; Nakagawa et al., 2005; Pike et al., 2005). An amount of 2 ml of each fraction was diluted by the addition of equal volume (2 ml) PBS and concentrated by ultrafiltration with Centricon30 (Amicon). Fractionated proteins were analyzed by Western blotting with each antibody. For the estimation of signal intensities, the rafts fraction (Fr. 1) in Figure 1B and the soluble fractions (Fr. 6) in Figures 1C,D were defined as 100%.
FIGURE 1
Statistical analysis
Statistical analyses were performed using Prism 9 (GraphPad Software) and Excel (Microsoft). Student’s t-tests or ANOVA followed by Tukey post-hoc test was used to compare groups. All data are expressed as mean ± standard error of the mean (SEM).
Results
Tyrosine phosphorylated GluA2 is concentrated in the lipid rafts fraction
To clarify the submembrane domain where tyrosine phosphorylated AMPA receptors localize, subcellular membrane fractionation was performed using Optiprep-density gradients. The method for the preparation of lipid rafts involves the extraction of crude membrane fraction from cultured cortical neurons in 0.5% Triton X-100, followed by separation of the low-density raft membranes in an Optiprep-density gradient (Figure 1A). Localization of Fyn PTK, as representative of palmitoylated Src family PTKs, and lipids raft-associated protein Caveolin-1 (Nabi and Le, 2003; Michel and Bakovic, 2007) were examined to confirm accurate isolation of lipid rafts domain (Figure 1A). Tyrosine phosphorylated GluA2 signals were majorly detected in fraction 1, corresponding to the lipid rafts fraction (Figure 1B, n = 3, p = 0.0020). Whereas most GluA2 proteins were detected in the detergent soluble fraction indicated as fraction 6 (Figure 1C, n = 3, p = 0.0004), tyrosine-phosphorylated GluA2 was remarkably concentrated in the lipid rafts fraction (Figure 1D, n = 3, p = 0.0315). GluA2 and its tyrosine phosphorylation signals retain at the undetectable level in Fractions 2–5.
Reduced GluA2 tyrosine phosphorylation by disruption of cholesterol-enriched membrane fraction
Filipin is an antibiotic polyene, which forms a complex with cholesterol in membranes and is widely used to disrupt lipid rafts in cells (Gimpl et al., 1997; Foster et al., 2003). Filipin is a mixture of four components, filipin I, II, III, and IV, and filipin III is the major component of the filipin complex, which provides a useful tool for studying the role of lipid rafts in cellular mechanisms (Lambert et al., 2006). Treatment of cultured neurons with filipin III blocks cholesterol-mediated endocytosis of membrane proteins (Auriac et al., 2010). As we previously showed (Hayashi and Huganir, 2004), stimulation of cultured cortical neurons with an agonist AMPA increases phosphorylation of GluA2 C-terminus at Tyr876 without affecting GluA2 protein expression amounts (Figure 2). Pretreatment of cortical neurons with filipin III significantly suppressed the AMPA-induced GluA2 tyrosine phosphorylation in cortical neurons [Figure 2, n = 4 each, ANOVA, F(3, 15) = 19.79, p = 0.0042].
FIGURE 2
Discussion
Src family PTKs-mediated phosphorylation of the AMPA receptor and subsequent exchange of GluA2-binding proteins play crucial roles in the endocytosis of GluA2-containing synaptic AMPA receptors (Hayashi and Huganir, 2004; Gladding et al., 2009; Hu et al., 2010; Yong et al., 2020). Src family PTKs are associated with gangliosides-containing lipid rafts prepared from the rodent brain (Kasahara et al., 1997, 2000). Our previous study showed that stimulation with AMPA induces the activation of AMPA receptor-associated Src family PTKs in cultured neurons (Hayashi et al., 1999). The experimental data presented here revealed that tyrosine phosphorylated-AMPA receptors are concentrated in lipid rafts (Figure 1). Moreover, GluR agonist stimulation-induced tyrosine phosphorylation of AMPA receptors occurs in a lipid rafts-dependent manner (Figure 2). Treatment with filipin III should disrupt the accumulation of AMPA receptors and Src family PTKs in the lipid rafts, which prevent subsequent Src family PTKs-mediated tyrosine phosphorylation of GluA2. Collectively, these results suggest that lipid rafts may provide a place for effective AMPA receptor tyrosine phosphorylation and they consequently enable receptor internalization from the synaptic surface.
We have previously shown that Src family PTKs-mediated tyrosine phosphorylation of GluA2 is detected in the cerebral cortex, hippocampus, and cerebellum of the intact mouse brain to a greater or lesser degree (Hayashi and Huganir, 2004). Moreover, stimulation with glutamate, AMPA, or N-methyl-D-aspartate (NMDA) upregulates GluA2 tyrosine phosphorylation and induces the following AMPA receptor internalization in cultured cortical neurons. The existence of signaling pathways is predictable, including AMPA receptors-, NMDA receptors-, and mGluRs-mediated activation of downstream Src family PTKs, whereas crosstalk among these signaling still remains unclear. Here, I showed that the lipid rafts are required for the most essential AMPA receptor-mediated tyrosine phosphorylation of GluA2 as a place of phosphorylation reaction. Future analysis will reveal the detailed upstream signaling, which regulates the activation and localization of Src family PTKs in the lipid rafts.
Covalent attachments of the most abundant saturated fatty acid, palmitate, to integral membrane receptors as well as to signaling molecules such as Src family PTKs are supposed to increase proteins’ affinity to lipid rafts (Linder and Deschenes, 2007; Fukata et al., 2016). Many neuronal receptors and ion channels are regulated by their reversible modification of the palmitoylation and depalmitoylation cycle (Kang et al., 2008; Shipston, 2011; Borroni et al., 2016; Hayashi, 2021a). In various modifications evolutionarily established in the vertebrate glutamatergic excitatory synapses, the most probable mechanism that forces AMPA receptors to translocate into lipid rafts microdomain is the palmitoylation of the receptors themselves (Hayashi et al., 2005; Matt et al., 2019; Hayashi, 2021a,b).
These findings offer a possible model that links tyrosine phosphorylation and palmitoylation of AMPA receptors as follows. Depalmitoylated AMPA receptors are trapped on synaptic action fibers through their binding with the 4.1N-spectrin protein complex and these unmodified AMPA receptors show stable surface expression (Figure 3A). Neuronal activity-induced palmitoylation of AMPA receptors should serve as a trigger for the translocation of the receptors to lipid rafts domain (Figure 3B). There, lipid rafts-enriched palmitoylated Src family PTKs phosphorylate GluA2 at Tyr876, followed by an exchange of GluA2-binding scaffolding proteins from GRIP1/2 to PICK1 and interaction with BRAG2, which accelerate AMPA receptor endocytosis (Figure 3C). Appropriate membrane localization of receptor proteins generally ensure dynamic regulation of the receptor functions in neurons. Our studies suggest the significance of crosstalk between two distinct signaling pathways, tyrosine phosphorylation and palmitoylation of AMPA receptors in compartmentalized synapses.
FIGURE 3
Statements
Data availability statement
The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author.
Ethics statement
The animal study was reviewed and approved by the Institutional Review Committees of Graduate School of Medicine, The University of Tokyo and National Institute of Advanced Industrial Science and Technology (AIST).
Author contributions
The author confirms being the sole contributor of this work and has approved it for publication.
Funding
This work was supported in part by the Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)/Japan Society for the Promotion of Science (JSPS) (Grant numbers 22680029 and 23650187), RRIME and FORCE from Japan Agency for Medical Research and Development (AMED) (Grant numbers JP18gm5910009 and JP20gm4010004), and the Takeda Science Foundation.
Acknowledgments
The author grateful to his colleagues for their valuable discussion, encouragement, and excellent administrative assistance.
Conflict of interest
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
1
AnggonoV.HuganirR. L. (2012). Regulation of AMPA receptor trafficking and synaptic plasticity.Curr. Opin. Neurobiol.22461–469. 10.1016/j.conb.2011.12.006
2
AureliM.GrassiS.PrioniS.SonninoS.PrinettiA. (2015). Lipid membrane domains in the brain.Biochim. Biophys. Acta18511006–1016.
3
AuriacA.WillemetzA.Canonne-HergauxF. (2010). Lipid raft-dependent endocytosis: A new route for hepcidin-mediated regulation of ferroportin in macrophages.Haematologica951269–1277. 10.3324/haematol.2009.019992
4
BorroniM. V.VallesA. S.BarrantesF. J. (2016). The lipid habitats of neurotransmitter receptors in brain.Biochim. Biophys. Acta18582662–2670.
5
CollingridgeG. L.IsaacJ. T.WangY. T. (2004). Receptor trafficking and synaptic plasticity.Nat. Rev. Neurosci.5952–962.
6
DieringG. H.HuganirR. L. (2018). The AMPA receptor code of synaptic plasticity.Neuron100314–329. 10.1016/j.neuron.2018.10.018
7
FosterL. J.De HoogC. L.MannM. (2003). Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors.Proc. Natl. Acad. Sci. U.S.A.1005813–5818. 10.1073/pnas.0631608100
8
FujitaA.ChengJ.HirakawaM.FurukawaK.KusunokiS.FujimotoT. (2007). Gangliosides GM1 and GM3 in the living cell membrane form clusters susceptible to cholesterol depletion and chilling.Mol. Biol. Cell182112–2122.
9
FukataY.MurakamiT.YokoiN.FukataM. (2016). Local palmitoylation cycles and specialized membrane domain organization.Curr. Top. Membr.7797–141.
10
GimplG.BurgerK.FahrenholzF. (1997). Cholesterol as modulator of receptor function.Biochemistry3610959–10974. 10.1021/bi963138w
11
GladdingC. M.CollettV. J.JiaZ.BashirZ. I.CollingridgeG. L.MolnarE. (2009). Tyrosine dephosphorylation regulates AMPAR internalisation in mGluR-LTD.Mol. Cell. Neurosci.40267–279. 10.1016/j.mcn.2008.10.014
12
HayashiT. (2021a). Post-translational palmitoylation of ionotropic glutamate receptors in excitatory synaptic functions.Br. J. Pharmacol.178784–797. 10.1111/bph.15050
13
HayashiT. (2021b). Evolutionarily established palmitoylation-dependent regulatory mechanisms of the vertebrate glutamatergic synapse and diseases caused by their disruption.Front. Mol. Neurosci.14:796912. 10.3389/fnmol.2021.796912
14
HayashiT.HuganirR. L. (2004). Tyrosine phosphorylation and regulation of the AMPA receptor by SRC family tyrosine kinases.J. Neurosci.246152–6160. 10.1523/JNEUROSCI.0799-04.2004
15
HayashiT.RumbaughG.HuganirR. L. (2005). Differential regulation of AMPA receptor subunit trafficking by palmitoylation of two distinct sites.Neuron47709–723. 10.1016/j.neuron.2005.06.035
16
HayashiT.UmemoriH.MishinaM.YamamotoT. (1999). The AMPA receptor interacts with and signals through the protein tyrosine kinase Lyn.Nature39772–76. 10.1038/16269
17
HeineM.ThoumineO.MondinM.TessierB.GiannoneG.ChoquetD. (2008). Activity-independent and subunit-specific recruitment of functional AMPA receptors at neurexin/neuroligin contacts.Proc. Natl. Acad. Sci. U.S.A.10520947–20952. 10.1073/pnas.0804007106
18
HenleyJ. M.WilkinsonK. A. (2016). Synaptic AMPA receptor composition in development, plasticity and disease.Nat. Rev. Neurosci.17337–350. 10.1038/nrn.2016.37
19
HeringH.LinC. C.ShengM. (2003). Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability.J. Neurosci.233262–3271. 10.1523/JNEUROSCI.23-08-03262.2003
20
HollmannM.HeinemannS. (1994). Cloned glutamate receptors.Annu. Rev. Neurosci.1731–108. 10.1146/annurev.ne.17.030194.000335
21
HuJ. H.ParkJ. M.ParkS.XiaoB.DehoffM. H.KimS.et al (2010). Homeostatic scaling requires group I mGluR activation mediated by Homer1a.Neuron681128–1142. 10.1016/j.neuron.2010.11.008
22
HuganirR. L.NicollR. A. (2013). AMPARs and synaptic plasticity: The last 25 years.Neuron80704–717. 10.1016/j.neuron.2013.10.025
23
InoueM.DigmanM. A.ChengM.BreusegemS. Y.HalaihelN.SorribasV.et al (2004). Partitioning of NaPi cotransporter in cholesterol-, sphingomyelin-, and glycosphingolipid-enriched membrane domains modulates NaPi protein diffusion, clustering, and activity.J. Biol. Chem.27949160–49171. 10.1074/jbc.M408942200
24
JiangJ.SuppiramaniamV.WootenM. W. (2006). Posttranslational modifications and receptor-associated proteins in AMPA receptor trafficking and synaptic plasticity.Neurosignals15266–282. 10.1159/000105517
25
KangR.WanJ.ArstikaitisP.TakahashiH.HuangK.BaileyA. O.et al (2008). Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation.Nature456904–909. 10.1038/nature07605
26
KasaharaK.WatanabeK.TakeuchiK.KanekoH.OohiraA.YamamotoT.et al (2000). Involvement of gangliosides in glycosylphosphatidylinositol-anchored neuronal cell adhesion molecule TAG-1 signaling in lipid rafts.J. Biol. Chem.27534701–34709. 10.1074/jbc.M003163200
27
KasaharaK.WatanabeY.YamamotoT.SanaiY. (1997). Association of Src family tyrosine kinase Lyn with ganglioside GD3 in rat brain. Possible regulation of Lyn by glycosphingolipid in caveolae-like domains.J. Biol. Chem.27229947–29953. 10.1074/jbc.272.47.29947
28
KesselsH. W.MalinowR. (2009). Synaptic AMPA receptor plasticity and behavior.Neuron61340–350.
29
LafontF.LecatS.VerkadeP.SimonsK. (1998). Annexin XIIIb associates with lipid microdomains to function in apical delivery.J. Cell Biol.1421413–1427. 10.1083/jcb.142.6.1413
30
LafontF.VerkadeP.GalliT.WimmerC.LouvardD.SimonsK. (1999). Raft association of SNAP receptors acting in apical trafficking in Madin-Darby canine kidney cells.Proc. Natl. Acad. Sci. U.S.A.963734–3738. 10.1073/pnas.96.7.3734
31
LambertS.Vind-KezunovicD.KarvinenS.GniadeckiR. (2006). Ligand-independent activation of the EGFR by lipid raft disruption.J. Invest. Dermatol.126954–962.
32
LinderM. E.DeschenesR. J. (2007). Palmitoylation: Policing protein stability and traffic.Nat. Rev. Mol. Cell. Biol.874–84. 10.1038/nrm2084
33
LindwasserO. W.ReshM. D. (2001). Multimerization of human immunodeficiency virus type 1 Gag promotes its localization to barges, raft-like membrane microdomains.J. Virol.757913–7924. 10.1128/jvi.75.17.7913-7924.2001
34
LuW.RocheK. W. (2012). Posttranslational regulation of AMPA receptor trafficking and function.Curr. Opin. Neurobiol.22470–479.
35
MattL.KimK.ChowdhuryD.HellJ. W. (2019). Role of palmitoylation of postsynaptic proteins in promoting synaptic plasticity.Front. Mol. Neurosci.12:8. 10.3389/fnmol.2019.00008
36
MichelV.BakovicM. (2007). Lipid rafts in health and disease.Biol. Cell99129–140.
37
MoffettS.BrownD. A.LinderM. E. (2000). Lipid-dependent targeting of G proteins into rafts.J. Biol. Chem.2752191–2198. 10.1074/jbc.275.3.2191
38
MoriH.MishinaM. (2003). Roles of diverse glutamate receptors in brain functions elucidated by subunit-specific and region-specific gene targeting.Life Sci.74329–336. 10.1016/j.lfs.2003.09.020
39
NabiI. R.LeP. U. (2003). Caveolae/raft-dependent endocytosis.J. Cell Biol.161673–677.
40
NadolskiM. J.LinderM. E. (2007). Protein lipidation.FEBS J.2745202–5210.
41
NakagawaT.MorotomiA.TaniM.SueyoshiN.KomoriH.ItoM. (2005). C18:3-GM1a induces apoptosis in Neuro2a cells: Enzymatic remodeling of fatty acyl chains of glycosphingolipids.J. Lipid. Res.461103–1112. 10.1194/jlr.M400516-JLR200
42
NeetK.HunterT. (1996). Vertebrate non-receptor protein–tyrosine kinase families.Genes Cells1147–169.
43
OliferenkoS.PaihaK.HarderT.GerkeV.SchwarzlerC.SchwarzH.et al (1999). Analysis of CD44-containing lipid rafts: Recruitment of annexin II and stabilization by the actin cytoskeleton.J. Cell Biol.146843–854. 10.1083/jcb.146.4.843
44
ParkinsonG. T.HanleyJ. G. (2018). Mechanisms of AMPA receptor endosomal sorting.Front. Mol. Neurosci.11:440. 10.3389/fnmol.2018.00440
45
PikeL. J. (2006). Rafts defined: A report on the keystone symposium on lipid rafts and cell function.J. Lipid. Res.471597–1598. 10.1194/jlr.E600002-JLR200
46
PikeL. J.HanX.GrossR. W. (2005). Epidermal growth factor receptors are localized to lipid rafts that contain a balance of inner and outer leaflet lipids: A shotgun lipidomics study.J. Biol. Chem.28026796–26804. 10.1074/jbc.M503805200
47
ReshM. D. (2016). Fatty acylation of proteins: The long and the short of it.Prog. Lipid. Res.63120–131. 10.1016/j.plipres.2016.05.002
48
SchnaarR. L. (2016). Gangliosides of the vertebrate nervous system.J. Mol. Biol.4283325–3336.
49
ScholzR.BerberichS.RathgeberL.KollekerA.KohrG.KornauH. C. (2010). AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression.Neuron66768–780. 10.1016/j.neuron.2010.05.003
50
SeeburgP. H. (1993). The TINS/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels.Trends Neurosci.16359–365.
51
ShepherdJ. D.HuganirR. L. (2007). The cell biology of synaptic plasticity: AMPA receptor trafficking.Annu. Rev. Cell. Dev. Biol.23613–643.
52
ShipstonM. J. (2011). Ion channel regulation by protein palmitoylation.J. Biol. Chem.2868709–8716.
53
SimonsK.VazW. L. (2004). Model systems, lipid rafts, and cell membranes.Annu. Rev. Biophys. Biomol. Struct.33269–295.
54
SmartE. J.YingY. S.MineoC.AndersonR. G. (1995). A detergent-free method for purifying caveolae membrane from tissue culture cells.Proc. Natl. Acad. Sci. U.S.A.9210104–10108. 10.1073/pnas.92.22.10104
55
TurnerM. S.SensP.SocciN. D. (2005). Nonequilibrium raftlike membrane domains under continuous recycling.Phys. Rev. Lett.95:168301. 10.1103/PhysRevLett.95.168301
56
YongA. J. H.TanH. L.ZhuQ.BygraveA. M.JohnsonR. C.HuganirR. L. (2020). Tyrosine phosphorylation of the AMPA receptor subunit GluA2 gates homeostatic synaptic plasticity.Proc. Natl. Acad. Sci. U.S.A.1174948–4958. 10.1073/pnas.1918436117
Summary
Keywords
AMPA receptor, Src family protein tyrosine kinase, palmitoylation, tyrosine phosphorylation, membrane, lipid rafts
Citation
Hayashi T (2022) Membrane lipid rafts are required for AMPA receptor tyrosine phosphorylation. Front. Synaptic Neurosci. 14:921772. doi: 10.3389/fnsyn.2022.921772
Received
16 April 2022
Accepted
11 October 2022
Published
31 October 2022
Volume
14 - 2022
Edited by
Akira Yoshii, University of Illinois at Chicago, United States
Reviewed by
Flavia Antonucci, University of Milan, Italy; Gareth Thomas, Lewis Katz School of Medicine at Temple University, United States
Updates
Copyright
© 2022 Hayashi.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Takashi Hayashi, takashi.hayashi@aist.go.jp
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